Open AccessReconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer
Author(s) -
Ji Young Kim,
Hyebin Lee,
Jongmin Jacob Woo,
Yue Wang,
Kwangsoo Kim,
Sukwoo Choi,
Ja June Jang,
Youngsoo Kim,
In Ae Park,
Dohyun Han,
Han Suk Ryu
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-03322-7
Subject(s) - nicotinamide , triple negative breast cancer , dna damage , breast cancer , dna repair , cancer research , biology , cell cycle , transcriptome , apoptosis , computational biology , dna , microbiology and biotechnology , chemistry , cancer , gene expression , biochemistry , gene , genetics , enzyme
Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair. We further elaborated the global interaction networks of molecular events via nicotinamide-inducible expression changes at the mRNA and functional protein levels. This approach indicated that nicotinamide treatment rewires interaction networks toward dysfunction in DNA damage repair and away from a pro-growth state in TNBC. To our knowledge, the high-resolution network interactions identified in the present study provide the first evidence to comprehensively support the hypothesis of nicotinamide as a novel therapeutic agent in TNBC.